Bone marrow "micrometastases" of epithelial tumors: detection and clinical relevance

The detection and elimination of "micrometastases" or, more precisely, isolated disseminated tumor cells or minimal residual disease is one of the main current topics in clinical oncology. Immunocytochemical and molecular, polymerase chain reaction (PCR) based methods are the preferred methods. Bone marrow as a mesenchymal organ and a frequent location for distant metastases is very suitable to study isolated disseminated tumor cells. Under optimal conditions one tumor cell among one million mononuclear bone marrow cells can be detected by immunocytochemistry or molecular methods. The specificity, however, varies significantly depending on the assay conditions used by each individual group, with false positive rates below 1% and over 80% reported. Immunocytochemistry with antibodies against different epithelial markers has shown that the presence of isolated disseminated tumor cells in bone marrow is an independent prognostic variable in breast, colorectal, gastric, and non-small cell lung cancer. Due to the lack of a standardized assay, however, comparison of the results between different groups is very difficult. Before the assessment for isolated disseminated tumor cells in bone marrow or other organs can be transferred into routine clinical practice, standardized methods have to be developed which must be tested in multicenter prospective trials.